Recent Advances in the Synthesis of Annelated 1,4-Benzodiazepines

This review describes the recent progress i n the syntheses of mono-and di-annelated I,4-benzodiazepiner with three, four, five,six and seven-membered rings fused t o different positions of I,@-benrodiarepine nucleus.While the chemistry of i,4-benrodiazepine derivatives has been comprehensively reviewed by various a ~t h o r s ' ~-' ~, no such review on the syntheees of annelated I,@-benzodiarepiner is available except a partial survey along with 1,5-benzodiazepiner, 1,3-benzcdiazepines and 2,4-ben~odiaze~ines'~'~~.Diannelated systems based on I,$-benzadiarepines are not given significant coverage in the latter.As such, the present article, covering all t h e available literature on mono-and diannelated 1,4-benzodiazepines has been prepared.In view of the voluminous d a t a available on the synthesis, chemistry and pharmacalogical properties of these derivatives, emphasis has been given t o t h e synthetic methodology in t h e present review.This review covers, methods reported in literature upto December, 1985.2. Mono-annelated I,&-bemodiazepines Compounds with three, four, five, six and seven-membered rings fused t o the different positions of 1,4-benzo-3.Three-membered rinxs annelated t o L,+benzodiarepines Only one example of this class -oxazirind2,3-dl [I,41benzodiarepme (17) is reported21-25.This is prepared by the photoiromeriration of the corresponding substituted 1,3-dihydro-2H-1,4-benrodiarepin-2-one-4oxides (16) (Scheme I). 4. Four-membered rings annelated t o I,4-benzodiarepines Novel aretd3,4-bl [1,4benzadiazepines (19) were obtained by ~h ~~~~~ by 40% alkali induced rearrangement of the adduct (181, prepared from chlardiazepoxide (2) and aliphatic aldehydes.The mechanism of the methyl migration into diazepine ring is not clear.Use of 10% sodium hydroxide in this reaction, 29 however, resulted in 1,5-benzodiazocine-5-oxides .Walter and ~r n i l i o ~' prepared aretobemcdiazepined i m e (21) by t h e cyclocondensation of L-2-aretidinecarboxylic acid with 5-chloroisatoic anhydride (20).A simple preparation of azetidina[l,2-dl [1,4!benrodiarepine (22) has been reported3' by the treatment of diazepam (3) with Et02CCH = C(Me)NHCH2C02K in the presence of triethylamine and phosphorus oxychloride (Scheme 2). 5. Five-membered rings annelated t o 1,4-benzdiarepines